Tityus serrulatus scorpion venom as a potential drug source for Chagas' disease: Trypanocidal and immunomodulatory activity.
Animals
Chagas Disease
/ drug therapy
Female
Immunomodulation
/ drug effects
Interleukin-6
/ metabolism
MAP Kinase Signaling System
/ drug effects
Macrophage Activation
/ drug effects
Macrophages
/ drug effects
Mice
Mice, Inbred C57BL
Nitric Oxide
/ metabolism
Scorpion Venoms
/ pharmacology
Scorpions
/ metabolism
Tumor Necrosis Factors
/ metabolism
Infectious disease
Macrophage
Mitogen-activated protein kinase (MAPK)
Peptides
Tityus serrulatus
Trypanosoma cruzi
Journal
Clinical immunology (Orlando, Fla.)
ISSN: 1521-7035
Titre abrégé: Clin Immunol
Pays: United States
ID NLM: 100883537
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
19
08
2020
revised:
19
01
2021
accepted:
06
03
2021
pubmed:
13
3
2021
medline:
25
6
2021
entrez:
12
3
2021
Statut:
ppublish
Résumé
Current chemical therapies for Chagas Disease (CD) lack ability to clear Trypanosoma cruzi (Tc) parasites and cause severe side effects, making search for new strategies extremely necessary. We evaluated the action of Tityus serrulatus venom (TsV) components during Tc infection. TsV treatment increased nitric oxide and pro-inflammatory cytokine production by Tc-infected macrophages (MØ), decreased intracellular parasite replication and trypomastigotes release, also triggering ERK1/2, JNK1/2 and p38 activation. Ts7 demonstrated the highest anti-Tc activity, inducing high levels of TNF and IL-6 in infected MØ. TsV/Ts7 presented synergistic effect on p38 activation when incubated with Tc antigen. KPP-treatment of MØ also decreased trypomastigotes releasing, partially due to p38 activation. TsV/Ts7-pre-incubation of Tc demonstrated a direct effect on parasite decreasing MØ-trypomastigotes releasing. In vivo KPP-treatment of Tc-infected mice resulted in decreased parasitemia. Summarizing, this study opens perspectives for new bioactive molecules as CD-therapeutic treatment, demonstrating the TsV/Ts7/KPP-trypanocidal and immunomodulatory activity during Tc infection.
Identifiants
pubmed: 33711450
pii: S1521-6616(21)00050-4
doi: 10.1016/j.clim.2021.108713
pii:
doi:
Substances chimiques
Interleukin-6
0
Scorpion Venoms
0
Tumor Necrosis Factors
0
Nitric Oxide
31C4KY9ESH
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108713Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.